Hydrocodone Bitartrate and Homatropine Methylbromide

HYDROCODONE BITARTRATE AND HOMATROPINE METHYLBROMIDE- hydrocodone bitartrate and homatropine methylbromide syrup
Atlantic Biologicals Corps

DESCRIPTION

This product contains hydrocodone (dihydrocodeinone) bitartrate, a semisynthetic centrally-acting narcotic antitussive. Homatropine methylbromide is included in a subtherapeutic amount to discourage deliberate overdosage.

Each teaspoonful (5 mL) for oral administration contains:

Hydrocodone Bitartrate, USP 5 mg

WARNING: May be habit forming.

Homatropine Methylbromide, USP 1.5 mg

Hydrocodone Bitartrate and Homatropine Methylbromide Syrup also contains: Caramel color, cherry flavor, citric acid, FD&C Red #40, methylparaben, propylparaben, purified water, sorbitol solution and sucrose syrup. Citric acid and/or sodium citrate may be added to adjust pH.

The hydrocodone component is a 4,5α-epoxy-3- methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5), a fine white crystal or crystalline powder, which is derived from the opium alkaloid, thebaine, has a molecular weight of (494.50) and may be represented by the following structural formula:

Homatropine methylbromide is 8-Azoniabicyclo [3.2.1]octane,3-[(hydroxy-phenylacetyl)oxy]-8, 8-dimethyl-,bromide,endo-; a white crystal or fine white crystalline powder, with a molecular weight of (370.29).

CLINICAL PHARMACOLOGY

Hydrocodone is a semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone, like other opium derivatives, will depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system are insignificant. Hydrocodone can produce miosis, euphoria, physical and physiological dependence.

Following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 ± 5.2 ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours and the half-life was determined to be 3.8 ± 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α-and 6-β-hydroxymetabolites.

INDICATIONS AND USAGE

Hydrocodone bitartrate and homatropine methylbromide syrup is indicated for the symptomatic relief of cough.

CONTRAINDICATIONS

Hydrocodone bitartrate and homatropine methylbromide syrup should not be administered to patients who are hypersensitive to hydrocodone or homatropine methylbromide.

WARNINGS

May be habit forming. Hydrocodone can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of hydrocodone bitartrate and homatropine methylbromide and it should be prescribed and administered with the same degree of caution appropriate to the use of other narcotic drugs (see ). DRUG ABUSE AND DEPENDENCE

Head Injury and Increased Intracranial Pressure

The respiratory depression properties of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.

Acute Abdominal Conditions

The administration of hydrocodone bitartrate and homatropine methylbromide or other narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Pediatric Use

In young pediatric patients, as well as adults, the respiratory center is sensitive to the depressant action of narcotic cough suppressants in a dose-dependent manner. Benefit to risk ratio should be carefully considered especially in the pediatric population with respiratory embarrassment (e.g., croup).

PRECAUTIONS

General

Before prescribing medication to suppress or modify cough, it is important to ascertain that the underlying cause of cough is identified, that modification of cough does not increase the risk of clinical or physiological complications, and that appropriate therapy for the primary disease is provided.

Special Risk Patients

Hydrocodone bitartrate and homatropine methylbromide should be given with caution to certain patients such as the elderly or debilitated, and those with severe impairment of hepatic or renal functions, hypothyroidism, Addison’s disease, prostatic hypertrophy or urethral stricture, asthma, and narrow-angle glaucoma.

Information for Patients

Hydrocodone may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient using hydrocodone bitartrate and homatropine methylbromide should be cautioned accordingly.

Drug Interactions

Patients receiving narcotics, antihistamines, antipsychotics, antianxiety agents or other CNS depressants (including alcohol) concomitantly with hydrocodone bitartrate and homatropine methylbromide may exhibit an additive CNS depression. When combined therapy is contemplated, the dose of one or both agents should be reduced. The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies of hydrocodone bitartrate and homatropine methylbromide in animals to evaluate the carcinogenic and mutagenic potential and the effect on fertility have not been conducted.

Pregnancy

: Pregnancy Category C: Animal reproduction studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide. It is also not known whether hydrocodone bitartrate and homatropine methylbromide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hydrocodone bitartrate and homatropine methylbromide should be given to a pregnant woman only if clearly needed. Teratogenic Effects

: Nonteratogenic Effects

Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.

Labor and Delivery

As with all narcotics, administration of hydrocodone bitartrate and homatropine methylbromide to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from hydrocodone bitartrate and homatropine methylbromide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.